Medicine on a small scale.

EMBO reports VOL 4 | NO 11 | 2003 ©2003 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION 1008 Over the past few years, nanotechnology has emerged as a new and exciting research field that deals with the design, synthesis and fabrication of structures at the molecular scale. Smallness is not in itself the prime goal; it is rather the expectation that, by manipulating matter at the molecular level, new intrinsic material properties can be created. Because living matter itself is basically composed of biological ‘nanomachines’ and nanostructures, researchers recognized quite early on that biology and medicine could be prime fields for the application of nanotechnology. In general, nanomedicine can be defined as the monitoring, repairing, construction and control of human biological systems at the cellular level by using materials and structures engineered at the molecular level. It encompasses much more than just being an extension of ‘molecular medicine’, and future products and developments may have extraordinary and far-reaching implications for the definition, diagnosis and treatment of disease, and for how medicine is practised (Freitas, 2002). The main interests currently lie in improving diagnostic methods and in developing better drug delivery systems to improve disease therapy. More generally, the scientific community is increasingly focusing its attention on the novel chemical and physical properties of nano-sized materials to develop new applications in regard to human health. Nanotechnology today deals mainly with two rather different but complementary types of material: nano-sized structures (or nanoparticles) and nanoporous materials. There are already some exciting developments in the field of diagnostics based on the use of nanoparticles, in particular fluorescent semiconductor quantum dots (QDs). QDs are monodisperse inorganic nanocrystalline particles made from semiconducting material and are typically 2–10 nm in size— about the size of a protein or a short sequence of DNA. They can be linked to biomolecules to form sensitive long-lived probes that target and identify specific cellular compounds (Fig. 1). As fluorescent probes, QDs have several advantages over conventional organic dyes: their emission spectra are narrow and symmetrical on the basis of their size and material composition, and they exhibit excellent photostability. In addition, they display broad absorption spectra, which makes it possible to excite many QDs to different colours with a single excitation light source (Wu et al., 2003). This is certainly an advantage in studying multiple biological targets simultaneously in the cell. The high photostability of QDs also allows real-time monitoring or tracking of intracellular processes in vivo over extended periods. Dubertret et al. (2002) showed this in a breakthrough experiment by labelling a living frog embryo with more than a billion individual QD particles encapsulated in phospholipid copolymer micelles. Their experiments showed that these QD micelles are non-toxic and stable in biological environments, which suggests the possibility of tracing cell lineages in embryogenesis experiments. Bioconjugated QDs have also been used for DNA hybridization and highthroughput genotyping of single-nucleotide polymorphisms (SNPs), the most common type of genetic variation between individuals. SNPs are very good markers for diseasecausing genes, and they hold further potential for personalized medicine as markers for differential drug responses (Xu et al., 2003). As the labelling of individual molecules or cell structures in living cells or tissues is becoming an increasingly important tool in diagnostics, QDs, because of their many Medicine on a small scale